Agroecology promises a third way between common global agriculture tradeoffs such as food production and nature conservation, environmental sustainability and ecosystem services. However, most successful examples of mainstreaming agroecology come from smallholder, family agriculture, that represents only about 30% of the world agricultural area. Mainstreaming agroecology among large scale farmers is urgently needed, but it requires addressing specific questions in research, technology and policy development to support sustainable transitions. Here we take stock of the existing knowledge on some key aspects necessary to support agroecological transitions in large scale farming, considering two contrasting starting points: highly subsidized and heavily taxed agricultural contexts, represented here by the examples of Western Europe and temperate South America. We summarize existing knowledge and gaps around service crops, arthropod-mediated functions, landscape and watershed regulation, graze-based livestock, nature-inclusive landscapes, and policy mechanisms to support transitions. We propose a research agenda for agroecology in large scale farming organized in five domains: (i) Breeding for diversity, (ii) Scalable complexity, (iii) Managing cycles beyond fields and farms, (iv) Sharing the cultivated landscape, and (v) Co-innovation with farmers, value chains and policy makers. Agroecology may result in a renewed impetus in large scale farming, to attract the youth, foster clean technological innovation, and to promote a new generation of large-scale farmers that take pride in contributing to feeding the world while serving the planet and its people.